Phase II Study of Vincristine Sulfate Liposome Injection (Marqibo) and Rituximab for Patients With Relapsed and Refractory Diffuse Large B-Cell Lymphoma or Mantle Cell Lymphoma in Need of Palliative Therapy

Vincristine (VCR) sulfate liposome injection (VSLI) plus rituximab, as palliative therapy for heavily pretreated, predominantly older, patients with advanced, relapsed, and refractory diffuse large B-cell lymphoma (DLBCL) and mantle cell lymphoma (MCL), was generally well tolerated and resulted in a meaningful overall response rate (ORR) of 59%, median response duration of approximately 5 months, and median overall survival (OS) of almost 11 months. The toxicity profile of this combination was predictable and manageable with limited hematologic toxicity. Background: VSLI (Marqibo) is active in advanced non-Hodgkin lymphoma (NHL) and untreated aggressive NHL. Because of its favorable hematologic toxicity profile, VSLI might be useful in patients unable to tolerate myelosuppressive therapies. Patients and Methods: Twenty-two patients with heavily pretreated, advanced CD20(+) DLBCL or MCL were treated with VSLI 2.0 mg/m(2), without a dose cap, every 2 weeks plus 4 weekly doses of rituximab 375 mg/m(2). OAR, complete response (CR), or partial response (PR), was the primary end point. Secondary end points included response duration, time to progression (TIP), and OS. Safety variables included adverse events and neurologic assessments. Results: The OAR was 13 of 22 (59%); 6 patients achieved a CR (27%), and 7 patients achieved a PR (32%). Median response duration, UP, and OS were 147 days, 121 days, and 322 days, respectively. The median number of VSLI doses was 5, the median individual VSLI dose was 3.5 mg, and the maximum cumulative VSLI dose was 43 mg. Grade 3 peripheral neuropathy, febrile neutropenia, and constipation were reported in 4, 2, and 1 patients, respectively. Conclusion: VSLI plus rituximab resulted in durable responses in patients with heavily pretreated advanced stage DLBCL and MCL. The toxicity profile was predictable and manageable with limited hematologic toxicity. Despite near-universal previous VCR exposure (96%) and doses of VSLI unachievable with standard VCR treatment, peripheral neuropathy and constipation were modest. This study supports further evaluation of VSLI as a component of DLBCL management. (C) 2014 Elsevier Inc. All rights reserved.